This invention relates to a method for the preparation of 3,4-difluorobenzoic acid. 3,4-difluorobenzoic acid has been prepared by the oxidation of the corresponding toluene derivative (G. Valkanas, J. Org. Chem., 27 (1962) 2923). More particularly, this invention relates to a process for the preparation of 3,4-difluorobenzoic acid by the decarboxylation of 4,5,-difluorophthalic anhydride or 4,5-difluorophthalic acid in which the decarboxylation reaction is conducted in N-methylpyrrolidone or dimethyl acetamide. Copper catalysts may be used in this reaction.
Many examples of decarboxylation reactions have been reported. Basic substances have been used to catalyze such reactions. For example, it is disclosed in D. S. Tarbell, et al Org. Syn., Coll. Vol. III (1955) 267, that 3,5-dichloro-4-hydroxybenzoic acid may be decarboxylated by vigorous heating in N,N-dimethylaniline. It is disclosed in A. Singer and S. M. McElvane, Org. Syn., Coll. Vol. II (1943) 214, that 3,5-dicarboxy-2,6-dimethylpyridine di-potassium salt may be completely decarboxylated by heating the salt in the presence of calcium hydroxide. Copper and copper salts have been used to catalyze decarboxylation reactions. For example, H. R. Snyder et al, Org. Syn., Coll. Vol. III (1955) 471 disclose the use of a copper oxide catalyst for the decarboxylation of imidazole 4,5-dicarboxylic acid.
Some compounds may be decarboxylated without catalysts. For example, C. Wang, Bul. Inst. Kim. Acad. Sinica, no. 2156 (1972), as abstracted in Chem. Abstracts (CA79 (15): 91729), discloses that tetrachloro or tetrabromophthalic acids, or their anhydrides, may be decarboxylated to the corresponding benzoic acids when refluxed in dimethyl formamide. 3-nitrophthalic acid underwent a similar reaction.
Decarboxylation is not always a predictable reaction. For example, A. S. Sultanov, J. Gen. Chem. (USSR) 16 1835 (1946) as abstracted in CA 41: 6223(e) discloses that salicylic acid may be decarboxylated by autoclaving the acid in the presence of copper bronze and benzene at 170.degree. C. The acid alone decarboxylates at 205.degree. C., while in the presence of aniline decarboxylation begins at 170.degree. C. In the case of salicylic acid, aniline and copper bronze seem to be equal in catalytic ability. On the other hand, when phthalic acid is heated in aniline at 180.degree. C., decarboxylation does not occur and instead phthalic anhydride is produced. Heating phthalic anhydride with copper bronze in chloroform at 180.degree. C. gave a 22% yield of benzoic acid. Phthalic acid was found to decarboxylate to yield benzoic acid merely by heating in water at 235.degree. C.
Decarboxylations of certain fluorophthalic acids have been reported. 3,4,5,6-tetrafluorophthalic acid decarboxylates under certain conditions to yield 2,3,4,5-tetrafluorobenzoic acid. For example, Japanese Patent JP 61/85349 A2[86/85349] as abstracted in Chem. Abstracts (CA105: 153719r), discloses that the reaction may be conducted in an aqueous medium at 150.degree. to 230.degree. C. The reaction may be carried out at a lower temperature (100.degree. to 250.degree. C.) in the presence of copper, zinc, cadmium, iron, cobalt, nickel, other oxides, hydroxides and/or carbonates. Japanese Patent Application 86/103,317 as abstracted in Chem. Abstracts (CA105 (22): 193368u), discloses that the above reaction may be conducted in an aqueous medium at a pH of 0.7-2.2 at a temperature of 100.degree.-200.degree. C. The pH of the medium is adjusted by acidifying with sulfuric acid and partial neutralization with calcium hydroxide. Japanese Patent 63/295529m A2[88/295529] as abstracted in Chem. Abstracts (CA 111 (3): 23221X), discloses that the reaction may be conducted at 130.degree. in tri-butylamine.
Yacobsen, O. J. discloses in Zh. Obsch. Khim. 36 (1966) page 139 (as appearing in Journal of General Chemistry of the U.S.S.R. translated from Russian 36 (1966) page 144), that 2,3,4,5-tetrafluorophthalic acid may be decarboxylated to yield 2,3,4,5-tetrafluorobenzoic acid by heating for one hour at 145.degree. C. in dimethyl formamide solvent.
Japanese Patent JP 01/52737 as abstracted in Chem. Abstract (CA)111 (14): 117305e discloses the preparation of 2,4,5-trifluorobenzoic acid by the decarboxylation of 3,4,6-trifluorophthalic acid in a liquid medium at a temperature of 80.degree.-250.degree. C.
Under slightly more vigorous conditions, Japanese Patent Application 61/43130 A2[86/43130] as abstracted in Chem. Abstracts (CA106 (1): 46295), discloses that 3,4,5,6-tetrafluorophthalic acid may be completely decarboxylated to 1,2,3,4-tetrafluorobenzene. The conditions for complete decarboxylation are in an aqueous medium from 210.degree. to 300.degree. C. with the optional presence of a catalyst.
Japanese Patent Application 86/290399 as abstracted in Chem. Abstracts (CA109 (19) 170038e), discloses that 3,5,6-trifluoro-4-hydroxyphthalic acid may be decarboxylated by heating the compound for three hours, in water, under nitrogen atmosphere, at 140.degree. C. (in a sealed tube) to yield 2,4,5-trifluoro-3-hydroxybenzoic acid.